Nuclear Protein Of The Testis Research Articles

NSD3 in Cancer: Unraveling Methyltransferase-Dependent and Isoform-Specific Functions.

NSD3 (nuclear receptor-binding SET domain protein 3) is a member of the NSD histone methyltransferase family of proteins. In recent years, it has been identified as a potential oncogene in certain types of cancer. The NSD3 gene encodes three isoforms, the long version (NSD3L), a short version (NSD3S) and the WHISTLE isoforms. Importantly, the NSD3S isoform corresponds to the N-terminal region of the full-length protein, lacking the methyltransferase domain. The chromosomal location of NSD3 is frequently amplified across cancer types, such as breast, lung, and colon, among others. Recently, this amplification has been correlated to a chromothripsis event, that could explain the different NSD3 alterations found in cancer. The fusion proteins containing NSD3 have also been reported in leukemia (NSD3-NUP98), and in NUT (nuclear protein of the testis) midline carcinoma (NSD3-NUT). Its role as an oncogene has been described by modulating different cancer pathways through its methyltransferase activity, or the short isoform of the protein, through protein interactions. Specifically, in this review we will focus on the functions that have been characterized as methyltransferase dependent, and those that have been correlated with the expression of the NSD3S isoform. There is evidence that both the NSD3L and NSD3S isoforms are relevant for cancer progression, establishing NSD3 as a therapeutic target. However, further functional studies are needed to differentiate NSD3 oncogenic activity as dependent or independent of the catalytic domain of the protein, as well as the contribution of each isoform and its clinical significance in cancer progression.

NUT carcinoma in pediatric patients: Characteristics, therapeutic regimens, and outcomes of 11 cases registered with the German Registry for Rare Pediatric Tumors (STEP).

Nuclear protein of the testis (NUT) carcinoma (NC) is a rare and highly aggressive tumor defined by the presence of a somatic NUTM1 rearrangement, occurring mainly in adolescents and young adults. We analyzed the clinical and biological features of German pediatric patients (≤18 years) with NC. This study describes the characteristics and outcome of 11 children with NC registered in the German Registry for Rare Pediatric Tumors (STEP). Eleven patients with a median age of 13.2 years (range 6.6-17.8) were analyzed. Malignant misdiagnoses were made in three patients. Thoracic/mediastinal tumors were found to be the primary in six patients, head/neck in four cases; one patient had multifocal tumor with an unknown primary. All patients presented with regional lymph node involvement, eight patients (72.7%) with distant metastases. Seven patients underwent surgery, eight radiotherapy with curative intent; polychemotherapy was administered in all patients. Novel treatment strategies including immunotherapy, targeted therapies, and virotherapy were applied in three patients. Median event-free survival and overall survival were 1.5 and 6.5 months, respectively. Every undifferentiated or poorly differentiated carcinoma should undergo testing for the specific rearrangement of NUTM1, in order to initiate an intense therapeutic regimen as early as possible. As in adults, only few pediatric patients with NC achieve prolonged survival. Thus, novel therapeutic strategies should be included and tested in clinical trials.

Pulmonary nuclear protein of the testis midline carcinoma:a case report

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare malignant epithelial tumor that typically occurs in the midline regions such as the head, neck, and mediastinum. This tumor is characterized by rapid development, aggressive growth, and strong invasiveness. Due to its short duration, most patients are diagnosed at advanced stages, often leading to rapid mortality. Although reports on pulmonary NUT carcinoma are uncommon, this article presents a case of pulmonary NUT carcinoma in which the patient repeatedly expectorated bronchial casts and tumor tissue. Additionally, a comprehensive review of relevant literature from recent years is provided to enhance understanding of this disease.

Metastatic NUT Carcinoma in a Child.

Nuclear protein of the testis (NUT) carcinoma is a rare and aggressive malignancy associated with rearrangements of the NUT gene on chromosome 15q14 .This entity is often under diagnosed and there is limited literature regarding its biology and optimal management. We report a case of pediatric NUT carcinoma presenting as a mass involving the nasal septum with associated bilateral cervical lymphadenopathy. CT and MRI of PNS revealed soft tissue lesion involving cartilaginous and bony septum and tip of nose .Histopathology of cervical lymph node and IHC with NUT confirmed the diagnosis of metastatic NUT carcinoma. NUT carcinoma has a dismal prognosis despite aggressive multimodality management. As new NUT targeting drugs using BET inhibitors are emerging, the correct and prompt recognition of NC is the key to improve patient outcome.

Relativity and the fine art of quality of life estimation

Nuclear protein of the testis (NUT) carcinoma (NC) is a rare type of poorly differentiated carcinoma. The median overall survival is 6.7–9.5 months. Surgery and radiotherapy are the main modalities of treatment. The efficacy of chemotherapy is often overlooked.A 7-year-old pediatric patient was diagnosed with recurrent NC of the submandibular gland, an uncommon site of NC. The tumor split and contracted following chemotherapy with cyclophosphamide, pirarubicin, cisplatin, ifosfamide, and etoposide. Subsequently, surgery was performed to excise the tumor with negative margins. Three months after the end of the multimodality treatment, the imaging did not show signs of recurrence or metastasis.The chemotherapy regimen of cyclophosphamide, pirarubicin, cisplatin, ifosfamide, and etoposide may be a new attempt to treat NC.

NUT Carcinoma in Children and Adolescents: The Expert European Standard Clinical Practice Harmonized Recommendations.

Nuclear protein of the testis ( NUT ) carcinoma (NC) is a rare and highly aggressive tumor mainly occurring in adolescents and young adults, defined by the presence of a somatic NUTM1 rearrangement. The aim is to establish internationally harmonized consensus recommendations for the diagnosis and treatment of adolescents and young adults with NC in the framework of the European Reference Network for Paediatric Oncology. The European Cooperative Study Group for Pediatric Rare Tumors developed recommendations according to the Consensus Conference Standard Operating procedure methodology and reviewed by external "experts." No evidence of level I to II exists. Recommendations were developed based on published prospective (level III), but more frequently retrospective series (level IV), case reports (level V), and personal expertise (level V). In addition, "strength" of recommendations were categorized by grading (grade A to E). Histology is mandatory for the diagnosis of NC, including immunolabeling with anti-NUT antibodies and molecular biology ( NUTM1 rearrangement) (level V; grade A). Treatment of NC usually combines aggressive approaches in multimodal regimens. Chemotherapy should be considered as first-line treatment (neoadjuvant vincristine-adriamycin-ifosfamide/cisplatin-adriamycin-ifsofamide or vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide) for unresectable or metastatic tumor (ie, 3 courses), rapidly followed by local treatment (level IV; grade B). Referral to a specialized surgical oncology center is highly recommended (level V; grade A). In localized NC, a complete microscopic surgical resection should be attempted whenever and as soon as possible, followed by primary irradiation (60 to 70Gy) and involved lymph nodes area (level IV; grade B). For head and neck tumors, a systematic neck dissection might be considered, even if N0 (level V; grade C). Adjuvant postirradiation chemotherapy is recommended, for a total of 9 to 12 courses (level IV; grade B). For first-line resected tumors, concomitant adjuvant chemotherapy to radiotherapy may be discussed (level IV; grade B). Targeted therapies and immunotherapeutic regimens should be delivered in the setting of prospective trials (level V; grade B). This project leads to a consensus strategy based on international experience with this very rare disease.

The contemporary management of cancers of the sinonasal tract in adults.

Sinonasal malignancies make up <5% of all head and neck neoplasms, with an incidence of 0.5-1.0 per 100,000. The outcome of these rare malignancies has been poor, whereas significant progress has been made in the management of other cancers. The objective of the current review was to describe the incidence, causes, presentation, diagnosis, treatment, and recent developments of malignancies of the sinonasal tract. The diagnoses covered in this review included sinonasal undifferentiated carcinoma, sinonasal adenocarcinoma, sinonasal squamous cell carcinoma, and esthesioneuroblastoma, which are exclusive to the sinonasal tract. In addition, the authors covered malignances that are likely to be encountered in the sinonasal tract-primary mucosal melanoma, NUT (nuclear protein of the testis) carcinoma, and extranodal natural killer cell/T-cell lymphoma. For the purpose of keeping this review as concise and focused as possible, sarcomas and malignancies that can be classified as salivary gland neoplasms were excluded.

Thyroid Carcinoma with NSD3::NUTM1 Fusion: a Case with Thyrocyte Differentiation and Colloid Production

In this report, we present a high-grade thyroid carcinoma with an NSD3::NUTM1 fusion detected on expanded next-generation sequencing testing. Nuclear protein of the testis (NUT) carcinomas comprise high-grade, aggressive tumors characterized by rearrangements of the NUTM1 gene with various partner genes, most commonly the bromodomain protein genes BRD4 and BRD3. Approximately 10% of NUT carcinomas contain an NSD3::NUTM1 fusion. NUT carcinomas manifest as poorly differentiated or undifferentiated squamous carcinomas, and 33% show areas of mature squamous differentiation. Only exceptionally have NUT carcinomas shown histology discordant from poorly differentiated/undifferentiated squamous carcinoma, and a thyroid NUT carcinoma with histologic thyrocyte differentiation has not been described to date. Our patient’s tumor exhibited mixed cytologic features suggestive of squamoid cells or papillary thyroid carcinoma cells. Overt squamous differentiation was absent, and the tumor produced colloid in poorly formed follicles. Immunophenotypically, the carcinoma was consistent with thyrocyte differentiation with expression of monoclonal PAX8, TTF1, and thyroglobulin (the last predominantly in extracellular colloid). There was zero to < 2% reactivity for proteins typically diffusely expressed in NUT carcinoma: p40, p63, and cytokeratins 5/6. NUT protein expression was equivocal, but fluorescence in situ hybridization confirmed a NUTM1 rearrangement. This exceptional case suggests that NUTM1 fusions may occur in an unknown number of aggressive thyroid carcinomas, possibly with distinctive histologic features but with thyrocyte differentiation. Recognition of this entity potentially has significant prognostic implications. Moreover, thyroid carcinomas with NUTM1 fusions may be amenable to treatment with NUT carcinoma-targeted therapy such as a bromodomain and extraterminal domain protein small molecular inhibitor (BETi).

Primary mediastinal germ cell tumours: an immunohistochemical and molecular diagnostic approach.

Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal neoplasms, and their diagnosis can be challenging, owing to small biopsy samples. The aim of this study was to develop a diagnostic algorithm using immunohistochemical staining, with a focus on novel markers, and molecular analysis of isochromosome 12p [i(12p)]. Paraffin-embedded tissues of 32 mediastinal tumours were analysed with immunohistochemical staining for sal-like transcription factor 4 (SALL4), Lin-28 homologue A (LIN28), octamer-binding transcription factor 3/4 (OCT3/4), D2-40, cluster of differentiation 117 (CD117), sex-determining region Y-box 17, sex-determining region Y-box 2 (SOX2), cluster of differentiation 30, the β-subunit of human chorionic gonadotropin (β-hCG), GATA-binding protein 3 (GATA3), forkhead box protein A2 (FOXA2), glypican-3 (GPC3), α-fetoprotein (AFP), terminal deoxynucleotidyl transferase (TdT), nuclear protein of the testis (NUT), and pan-cytokeratin. Quantitative real-time polymerase chain reaction was performed to investigate the i(12p) status. Fifteen seminomas, seven teratomas, one yolk sac tumour, one choriocarcinoma and seven mixed PMGCTs were diagnosed. Each entity had different immunohistochemical staining patterns, which helped to distinguish them: OCT3/4, D2-40, CD117 and TdT for seminoma; OCT3/4 and SOX2 for embryonal carcinoma; FOXA2, GPC3 and AFP for yolk sac tumour; and β-hCG and GATA3 for choriocarcinoma. Mature teratomas stained positively for pan-cytokeratin in epithelial components and focally for SALL4, SOX2, GATA3, D2-40, and FOXA2. Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed, showing strong nuclear SOX2 staining and speckled nuclear NUT staining. i(12p) was detected in 24 of 27 PMGCTs (89%). A diagnostic algorithm is of great importance for a reliable diagnosis of PMGCT in, usually small, tissue biopsy samples. Therefore, a combination of three to four antibodies to identify the correct histological subtype is usually necessary, in addition to morphological features. The i(12p) status serves as an additional option to indicate a germ cell origin in selected cases.

Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma.

IntroductionPulmonary nuclear protein of the testis (NUT) midline carcinoma (NMC) is a aggressive cancer with t (15, 19) translocation. Here we present the clinicopathological characteristics and molecular genetics alterations of primary pulmonary NMC.MethodsFluorescence in situ hybridization (FISH) assay was performed to evaluate NUT translocation. Next generation sequencing (NGS) was performed to investigate genomic landscape. A panel of 289 lung cancer tissues with undifferentiation was retrospectively screened for NUT expression by immunohistochemical (IHC) assay.ResultsOverall, 2136 lung cancer samples were reviewed. We consecutively identified 12 cases of primary pulmonary NMC. Computed tomography revealed centrally located bulky lung mass with ipsilateral mediastinal lymph node and pleural involvements. Tumor cells presented diffuse poor differentiation and focal squamous differentiation with positive NUT expression. NUT rearrangement was confirmed by FISH assay. Ten NMC samples were investigated by NGS. The most common alterations identified were P53, PIK3CA, AUTS2, ITIH2, and CDKL5 genes. Pulmonary NMC exhibited increased activity of PI3K/AKT pathway. In the screening study, BRD4‐NUT rearrangement was identified in two cases.ConclusionNUT rearrangement remains the gold standard in the diagnosis of pulmonary NMC. PI3K inhibition is a potential targeted therapy for pulmonary NMC.

Understanding the Patient Experience in NUT Carcinoma: Qualitative Interviews with Patients and Caregivers to Develop a Conceptual Framework.

IntroductionNUT (nuclear protein of the testis) carcinoma (NUTca) is a rare and aggressive cancer that is genetically hallmarked by a chromosomal abnormality in the NUT gene, and presents with tumors in the head, neck, and lungs. Currently there is no standard of care, but patients may undergo surgery, radiation, and/or chemotherapy. There is a lack of published research describing the patient experience of NUTca. The objective of this study was to develop a conceptual framework (CF) that describes patients’ experience of NUTca to inform the selection of outcome measures and design of patient-centric endpoints for future clinical research.MethodsIndividual, semi-structured telephone interviews were conducted with patients and caregivers of patients who have/had NUTca (caregivers interviewed due to recruitment challenges resulting from the rarity of NUTca). Participants were asked about their disease symptoms, impacts, and treatment experience. Interviews were audio-recorded, transcribed, and analyzed using inductive coding. The CF was developed through inductive categorization of concepts, sub-domains, and domains.ResultsTwenty-seven interviews were completed (patients n = 10; caregivers n = 17). Participants reported systemic symptoms (e.g., fatigue) and symptoms related to the location of the tumor (e.g., nose blockage for head/neck tumor). Pain emerged as an important and bothersome symptom across tumor locations. Participants reported impacts on their daily activities (e.g., showering), emotions (e.g., preoccupation), sleep, social life (e.g., isolation), roles (e.g., caring for children), and finances. The final CF was organized into four symptom domains [systemic, location-specific (head/neck, lung), pain, and digestive] and six impact domains (daily activities, emotional, sleep, social, role, and financial).ConclusionsThis study describes the patient experience of NUTca and proposes an evidence-based CF that informs both the clinical community’s understanding of the disease and selection of a patient-reported outcome (PRO) measure to assess treatment benefit in future NUTca trials.

Clinical, Radiographic, Pathologic Characterization and Survival Outcomes of Nuclear Protein of the Testis Carcinoma.

Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor with characteristic BRD4-NUTM1 translocation and a poor prognosis. The primary objective of this study was to describe the clinical and radiologic features, treatment response, and survival of NUT carcinoma (NC). This retrospective single-center study was based on the review of medical records of NC patients with a specific genetic rearrangement or positive anti-NUT nuclear staining. Overall survival (OS) was analyzed according to primary tumor location. This series of 22 patients had a mean age of 36.27 ± 2.68 years with 68% women and 32% men. The median age at diagnosis was 34 years (range, 17-55 years). The primary tumor was located in the chest (n = 12/22; 55%), head and neck (n = 9/22; 40%), and 1 patient had a renal tumor. About 68% (n = 15/22) patients presented with regional lymph nodal involvement and 77% (n = 17/22) had distant metastases. All the bone metastases were lytic (100%) with mixed lytic and sclerotic metastases in 5 patients. Only 18% (n = 4/22) of the patients showed response to treatment, with progression in the remaining 18 patients. The median OS was 7 months. The OS was significantly (P = 0.024) more in patients with primary head and neck NC (n = 9; OS, 16 months) versus those with pulmonary and other locations (n = 13; OS, 6 months). Nuclear protein of the testis carcinoma is an aggressive disease refractory to conventional therapy. Imaging with the complementary use of computed tomography, magnetic resonance imaging, and positron emission tomography/computed tomography is important for staging, guiding management, assessing the treatment response, and surveillance.

Therapeutic targeting of p300/CBP HAT domain for the treatment of NUT midline carcinoma

Nuclear protein of the testis (NUT) midline carcinoma (NMC), is a rare and highly aggressive form of undifferentiated squamous cell carcinoma. NMC is molecularly characterized by chromosomal rearrangement of the NUT gene to another gene, most commonly the bromodomain and extraterminal domain (BET) gene BRD4, forming the BRD4-NUT fusion oncogene. Therefore, inhibiting BRD4-NUT oncogenic function directly by BET inhibitors represents an attractive therapeutic approach but toxicity may limit the use of pan-BET inhibitors treating this cancer. We thus performed a drug screening approach using a library consisting of epigenetic compounds and ‘Donated Chemical Probes’ collated by the Structural Genomics Consortium (SGC) and identified the p300/CBP HAT inhibitor A-485, in addition to the well-known BET inhibitor JQ1, to be the most active candidate for NMC treatment. In contrast to JQ1, A-485 was selectively potent in NMC compared to other cell lines tested. Mechanistically, A-485 inhibited p300-mediated histone acetylation, leading to disruption of BRD4-NUT binding to hyperacetylated megadomains. Consistently, BRD4-NUT megadomain-associated genes MYC, CCAT1 and TP63 were downregulated by A-485. A-485 strongly induced squamous differentiation, cell cycle arrest and apoptosis. Combined inhibition of p300/CBP and BET showed synergistic effects. In summary, we identified the p300/CBP HAT domain as a putative therapeutic target in highly therapy-resistant NMC.

Nuclear protein of the testis midline carcinoma in the oral cavity: retrospective review of those initially diagnosed as poorly differentiated squamous cell carcinoma using an anti-C52B1 antibody

Nuclear protein of the testis (NUT) midline carcinomas (NMC) are malignant epithelial tumours that have chromosomal rearrangements of the gene encoding NUT at 15q14. NMC is typically an aggressive fatal cancer, clinically overlaps with other carcinomas, and differential diagnosis is difficult. The purpose of this study was to investigate NMC in poorly differentiated oral squamous cell carcinoma (OSCC) with a retrospective analysis based on anti-C52B1 immunohistochemical staining. An anti-C52B1 antibody was used for immunohistochemical staining in all 27 primary tumours, and the prevalence and pathological features of NMC in the oral cavity were examined. Only two of 27 cases (7.4%) were C52B1 immunopositive. Both positive patients were women aged 38 and 43 years — younger than the other C52B1-negative patients, whose average age was 65.6 years (range 41–83). The primary sites were the right side of the floor of the mouth and the left side of the tongue. They had a poor prognosis and died within 8 months postoperation compared with the median overall survival time of 60.2 months for patients with other poorly differentiated squamous cell carcinoma. The pathological findings of their primary tumours were similar to typical poorly differentiated OSCC.

NUT Midline Carcinoma of the Lung in a Six-Year-Old Child

ABSTRACTBackground: Nuclear protein of the testis (NUT) midline carcinoma is genetically defined by rearrangement of NUT or by immunohistochemical expression of NUT. Findings: A 6-year old child had a NUT midline carcinoma of the lung. Despite aggressive therapy, the child died. Conclusion: NUT carcinoma, which can be diagnosed immunohistochemically, remains an aggressive tumor.

NUT carcinoma in children and adults: A multicenter retrospective study.

Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer is underdiagnosed and poorly treated. The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy. This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti-NUT nuclear staining (>50%). This series of 12 patients had a median age of 18.1 years (ranges: 12.3-49.7 years). The primary tumor was located in the chest in eight patients, the head and neck in three patients, and one patient had a multifocal tumor. Nine patients presented regional lymph node involvement and eight distant metastases. One-half of patients were initially misdiagnosed. Specific NUT antibody was positive in all cases tested. A transient response to chemotherapy was observed in four of 11 patients. Only two patients were treated by surgery and five received radiotherapy with curative intent. At the end of follow-up, only one patient was still in remission more than 12 years after the diagnosis. Median overall survival was 4.7 months (95% confidence interval [CI]: 2.1-17.7). NUT carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of NUT gene is useful to propose the optimal therapeutic strategy.

Hilar/endobronchial NUT midline carcinoma: A case report

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare aggressive tumor described in the midline in the chest and head and neck. Initially reported in younger individuals, it has subsequently been shown to have a wider age distribution. The defining feature of these tumors is its association with BRD-NUT rearrangements. Occasionally NMC has been observed in a non-midline location. This case report describes an unusual rapidly progressing non-midline hilar/endobronchial location of an NMC in a 34-year-old man. The clinical and histologic features were that of an undifferentiated neoplasm concerning for a small cell carcinoma or a lymphoma. A broad panel of immunohistochemical markers for carcinoma, lymphoma and melanoma were negative which led us to suspect a diagnosis of NMC. A positive immunostaining with p63 and NUT protein antigen confirmed the diagnosis. The p63 positivity and cytokeratin negativity suggest a primitive/precursor squamous cell derivation.

Clinicopathological Features in Young Patients Treated for Small-Cell Lung Cancer: Significance of Immunohistological and Molecular Analyses

BackgroundSmall-cell lung cancer in young patients is very rare and has not been adequately described. In addition, malignancies associated with genetic rearrangements of nuclear protein of the testis (NUT) have been reported in young patients. Patients and MethodsWe reviewed the clinical records of patients younger than 40 years of age who had been diagnosed as having SCLC and had been treated for this condition. We also examined NUT rearrangements using immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH) analysis. ResultsWe evaluated the diagnoses and treatment outcomes of 8 young patients among 747 SCLC patients. Based on further analyses using IHC staining and FISH, NUT rearrangements were found in 2 of these cases. The range of the overall survival period was 3.6 to 49.7 months. The 2 patients with NUT rearrangements survived for less than 12 months. ConclusionNUT rearrangements were identified in 2 patients who had been previously diagnosed as having SCLC. Further attention regarding the diagnosis of SCLC in young patients is needed.

NUT Midline Carcinoma

In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia.

A Review of NUT Midline Carcinoma

Nut midline carcinomas are uncommon carcinomas characterized by chromosomal rearrangements that involve the gene encoding the nuclear protein of the testis (NUT). This article reviews the clinicopathologic features of these malignancies. Ancillary testing is discussed as well as the pathologic differential diagnosis.